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Insulin signaling and reduced glucocorticoid receptor activity attenuate post-prandial gene expression in liver

ABSTRACT: C57BL/6J mice were subjected to night restricted feeding (ZT12-ZT24) and livers were isolated immediate before (ZT10) and after feeding (ZT14). Combined RNA-seq, DNase-seq and H3K27Ac ChIP-seq identified hundreds of genes and enhancers regulated by acute feeding. Importantly, this feeding regulated transcriptional program follows similar rhythmic expression patterns as the intrinsic circadian transcriptional programs. ChIP-seq showed that feeding repressed enhancers were occupied by both GR and FOXO1 and occupancy of these factors were suppressed by feeding correlating with increased insulin levels and reduced corticosterone levels. Interestingly, despite considerable genome-wide overlap between GR and FOXO1, injection of dexamethasone (dex) or insulin receptor antagonist (S961) immediately before feeding, demonstrated that the glucocorticoid and insulin receptor pathways control distinct transcriptional programs. And strikingly, only combined dex and S961 treatment reversed feeding induced changes to most of the hepatic transcriptome. These corticosteroid and insulin regulated transcriptional programs are dysregulated in diet-induced obese animals.

ORGANISM(S): Mus musculus

PROVIDER: GSE119713 | GEO | 2018/11/01

REPOSITORIES: GEO

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